Understanding Direct-to-Consumer Genetic Testing: Look Before Leaping

A Report from PDF's Medical Policy Committee

The growing availability of genetic testing to individuals, called Direct-to-Consumer (DTC) testing, has generated considerable interest in the Parkinson’s disease (PD) community. Briefly described, genetic testing services can be used by individuals — without consultation with a medical doctor or geneticist — in an attempt to find out whether they are at risk of developing Parkinson’s disease and other health conditions, or, if they have already been diagnosed with PD, what may have caused it.

While PDF supports the right of any individual to learn (or decide against knowing) their own genetic information, we think it is important to point out some of the potential challenges that a person may experience and what an individual should consider before buying a test.

One challenge is that the results of DTC genetic testing can be misinterpreted and misleading. DTC tests that are currently available analyze only a handful of known Parkinson’s-related genes. If the tests turn out negative, a person still cannot be assured that he or she is not at risk of developing the disease. Further, a positive result is not a guarantee that someone will develop PD.

Alternatively, the tests results may provide information on the risk of developing other diseases or conditions that will have significant implications not just for the person being tested but also for his or her immediate family members. Such information can be put in context by a physician or genetic counselor.

The report below by PDF’s Medical Policy Committee is designed to provide advice to people who may be considering purchasing a genetic test. Here is a summary of its main recommendations:

Recruit the support of your physician or a genetic counselor as a partner in making the decision to be tested. The issues are scientifically complex and have potential implications for yourself as well as your family members.

Be aware of what the test can and cannot say about your health. View sample reports provided by the company to understand what information is actually provided. Because the genetics of Parkinson’s is ever-evolving, be sure to check that the scientific evidence on which a test is based is current and clearly stated.

Know how your personal information will be kept private. Genetic information from consumer tests do not have the same privacy protections as do physician ordered tests.

For additional information, browse the full report below, or call PDF's toll-free HelpLine at (800) 457-6676. Please note that this report was drafted in conjunction and consultation with members of the PDF Medical Policy Committee by Roy Alcalay, M.D., PDF Research Center at Columbia University Medical Center, New York, NY, and Christopher Goetz, M.D., PDF Research Center at Rush University Medical Center, Chicago, IL, and reviewed by PDF's People with Parkinson's Advisory Council.

Understanding Direct-to-Consumer Genetic Testing: Look Before Leaping

Introduction

In recent years, there has been frequent discussion in the Parkinson’s disease community about Direct-to-Consumer (DTC) genetic testing, also known as at-home genetic test programs. These services are designed to allow individuals to access their genetic information without necessarily involving a medical professional in the process. These programs are marketed directly to consumers most commonly via television, Internet, magazines or newspapers. Customers typically provide a saliva sample or a cotton swab of their mouth by mail to the gene testing company, and in due course, they receive a genetic analysis either online or by mail. In most instances, the analysis provides information on the probability or risk of developing one or more potential medical conditions, including Parkinson’s disease. Typically, DTC genetic testing provides consumers with two basic types of information:

For those with an already-diagnosed condition, such as Parkinson’s disease, genetic testing may tell them about variations in their genes which have been shown to confer a level of risk for developing the disease they already have.

For those who are concerned about the future risk of developing a disease, genetic tests may be able to identify whether they have gene variations known to confer an increased disease risk in comparison to people without that gene pattern.

PDF has been approached on numerous occasions by people with Parkinson’s disease to guide them on how they should approach DTC genetic testing opportunities. To meet that need, the PDF Medical Policy Committee has reviewed available information on this topic and examined an array of materials from past and existing DTC genetic testing programs, including 23andMe, deCODEme and Navagenics. The results of that review are below and are divided into two major parts: the first addresses what consumers should know before using DTC genetic testing and the second focuses on DTC testing in the field of Parkinson’s disease based on the currently available scientific data.

I. General Recommendations on Using Direct-to-Consumer Genetic Testing

In addressing how people with Parkinson’s disease and their families can best place the issues surrounding genetic testing into context and to make good decisions, the PDF Medical Policy Committee considers a particularly important document to be the 2008 American College of Medical Genetics (ACMG) Statement on DTC genetic testing. In this document, experts emphasize that a set of five minimal criteria must be met before a DTC program can be considered for recommendation. Because access to such programs are consumer-initiated, consumers themselves must take the responsibility to ensure that they are comfortable with the answers to these points. Below are listed the five points from the ACMG Statement with recommendations from the PDF Medical Policy Committee.

1. A knowledgeable health care professional is recommended to be involved in the process of ordering and interpreting a genetic test. The marketing aim of DTC genetic tests is to empower individuals with direct access to their own health information. Yet even though these tests are targeted to consumers, the PDF Medical Policy Committee has found the interpretation of their results remains complex. Therefore, the PDF Medical Policy Committee strongly recommends those interested in this information to discuss DTC gene testing with a physician or a genetic counselor before embarking on participation in a program.

Often, physicians will recommend and refer you to a genetic counselor as a first step. Genetic counselors are specialists who are trained to educate you and your family on the implications of gene testing. They work closely with you and your physician and are ready to address questions before participation and especially after any report is delivered. (To find a genetic counselor, contact the National Society of Genetic Counselors.)

In sum, the PDF Medical Policy Committee believes that by partnering with your physician or a genetic counselor you will be best prepared to not only fully understand the information from any genetic test, but also be fully informed as to whether such testing is even the right course of action for you.

2. Consumers should be fully informed regarding what the test can and cannot say about their health. It is essential that everyone understand exactly what type of information will be received before actually purchasing or participating in DTC genetic testing. To do so, consumers should ask for a sample genetic test report from the company. As recommended above, it is a good idea to share it with your physician or genetic counselor and together determine what type of added expertise is likely to be needed in order to make the participation in the program fruitful. You should also understand the potential implications of your test results not only for you but also for other family members. Devise a plan in advance on how you will manage the results and their impact on you and your family.

The PDF Medical Policy Committee also recommends that prospective participants study all materials from companies dealing with DTC genetic testing to make certain that they are comfortable with and understand what is presented. In reviewing sample materials from DTC companies, the PDF Medical Policy Committee members consider that the currently available consumer materials often fall short of clearly providing comprehensive information for potential participants. These issues are scientifically complex, and, because the testing is initiated by consumers themselves, the PDF Medical Policy Committee stresses that individuals must make it their responsibility to be educated and informed.

The best way to become educated is to seek help from your physician or a genetic counselor. The issues outlined above will be covered by discussions between you, your family and your physician or genetic counselor. Meetings with a genetic counselor before taking a genetic test allows time for planning on how the results will impact people involved — medically, emotionally and psychologically.

3. The scientific evidence on which a test is based should be clearly stated and easily understood. DTC genetic testing programs usually examine a wide array of genes, and the scientific importance of one gene pattern for detecting the risk of disease may be very different from another. Because both genetic studies and their applicability to Parkinson’s disease are ever-evolving, each test available should offer up-to-date and accurate information in language appropriate to individuals and families. The scientific evidence for each genetic test that forms the panel being purchased or acquired needs to be documented so that consumers can rationally decide on whether to participate and whether the test results will satisfactorily address their questions. The PDF Medical Policy Committee did not find this criterion to be well met in its review of many DTC programs.

4. The clinical testing laboratory must be accredited by acknowledged accrediting agencies. As in any scientific endeavor, the quality of the data dictates the power of the observation. Consumers must take the responsibility to ensure that any program they select operates under legitimate and high quality standards. Congress passed the Clinical Laboratory Improvement Amendments (CLIA) in 1988 to establish standards of quality for all laboratory testing, including accuracy and reliability. To ensure these standards are met, several accreditation organizations oversee the issuance of certificates of compliance. These credentials should be available on the company or program website and printed materials.

5. Privacy concerns must be addressed. The PDF Medical Policy Committee is sensitive to the protection of patient privacy and supports the limits imposed by the Genetic Information Nondiscrimination Act to limit the risk of bias by insurance companies, work place officials, or other agencies that may gain access to DTC genetic information. Because this information is acquired by individuals themselves without a doctor’s prescription, it is not automatically protected in the same way as medical information obtained by physicians related to their patients’ care. The PDF Medical Policy Committee again stresses to consumers that they need to be very well informed on how their genetic information and their identity will be stored, protected, and potentially shared privately or publicly.

II. Direct-to-Consumer Genetic Testing for Parkinson’s Disease

The genetics of PD is quite complex and knowledge is evolving on a daily basis. While the genetic testing available through DTC testing can be extensive, it does not cover all genes and all mutations known currently to be linked to Parkinson’s disease. Further, genetic results, whether positive or negative, can be quite involved in terms of their interpretation. The following points address the value of DTC testing for two categories of potential consumers: people who have Parkinson’s disease and people who do not but are concerned about their Parkinson’s disease risk.

People with Parkinson’s Disease
Two reasons commonly voiced why a person with Parkinson’s disease wants to engage in DTC genetic testing is to attempt to seek information that can be used to personalize or to modify their current Parkinson’s treatment or they seek genetic testing to understand what genetic factors may have influenced their developing the disease. Unfortunately, marketing claims of current testing services do not match with the realities of current clinical practice nor the scientific understanding as to the genetic causes of Parkinson’s disease.

At present, the available scientific data on the genetics of Parkinson’s disease do not provide very useful clinical information that materially influences or alters patient treatment. This includes information gathered from the type of extensive genetic analysis only performed in a scientific laboratory setting. The Parkinson’s-related information available through DTC genetic testing companies is much less extensive and those results are from the analysis of a small subset of known Parkinson’s genes and risk factors. Simply put, genetic testing for Parkinson’s disease does not currently provide physicians with any insights related to disease manifestations, treatment or long-term disease progression.

For others seeking to understand the genetic factors relating to how they developed Parkinson’s disease, it is important to realize that only a small percentage of people (~10 percent) have a directly identifiable genetic cause to their disease. For instance, one of the most commonly associated genes with Parkinson’s is LRRK2. Mutations in this gene are thought to be found in only 1-2 percent of sporadic cases of Parkinson’s, the number is slightly higher in familial cases, and up to 30 percent in those of North African or Ashkenazi descent (Wider et al. 2010).

There will be a rare instance when someone does have a currently identifiable genetic cause to their Parkinson’s disease. One should appreciate that this knowledge may have implications to family members who may or may not want to know the information (see discussion below). As a result, the PDF Medical Policy Committee encourages people with Parkinson’s disease considering DTC testing to discuss this with their physician or genetic counselor before purchasing a DTC genetic test. Your health care professional will discuss the implications of a given positive or negative test not only for you but also for other family members. Specifically, prior to enrolling in such programs, individuals will want to contemplate whether they plan on sharing the information they receive with their children or their own siblings.

People without Parkinson’s Disease
The vast majority of people who use DTC testing are not affected by Parkinson’s disease. Among DTC genetic testing consumers, many consider themselves at an increased risk for Parkinson’s disease; for example, they may have a first degree relative with Parkinson's disease. As discussed above, there are very few individuals for whom genetic testing, even when done at scientific laboratories, can identify a genetic mutation that is likely to substantially alter their risk of developing Parkinson’s disease. The main limitation here is scientific — there remains much to be learned about the genetic factors of Parkinson’s disease. Therefore, because the genetics of Parkinson’s disease is not completely known, negative genetic test results cannot remove the possibility of developing Parkinson’s disease some time in the future.

For a few individuals, genetic testing, even using the limited DTC genetic testing available, will reveal the presence of genes that have been identified to confer a much higher risk for Parkinson's disease, namely mutations in the LRRK2 or GBA genes. A mutation in either gene does not definitively lead to Parkinson’s disease — the results are not black and white but are shades of gray. In general, the majority of people with these mutations will not develop Parkinson’s disease. A better way to interpret these results is to recognize that they only confer a probability rate that for most people equates to about a 30 percent risk of developing the disease, but will vary based upon one’s ethnic background. In addition, these test results provide absolutely no information as to when Parkinson’s disease will eventually develop in those who will.

In addition, positive results in genes that confer a very low risk for Parkinson's disease are common among people who will never develop Parkinson's disease. Another way to put these potential results in perspective is remember that Parkinson’s disease remains relatively uncommon — everyone has a ~1 percent chance of developing the disease. Therefore, even risk factors that double one’s likelihood of developing Parkinson’s disease to 2 percent still means it is very unlikely one will actually ever develop the condition.

Summary

At the present, DTC genetic testing places a wealth of information directly in the hands of consumers; however, no program reviewed by the PDF Medical Committee adequately prepares consumers with the knowledge that is necessary to appropriately interpret results and to counsel them on its implications to themselves and their families. Therefore the PDF Medical Policy Committee recommends that consumers follow these three guidelines before making a decision to participate: 1. Review the PDF Medical Policy Committee recommendations above and understand their implications. 2. Recruit the support of your physician as a partner in making the decision to participate in these programs. 3. If recommended, seek formal genetic counseling to help decide whether to participate and to help interpret any results you may receive.

Report drafted in conjunction and consultation with members of the PDF Medical Policy Committee by Roy Alcalay, M.D., PDF Research Center at Columbia University Medical Center, New York, NY, and Christopher Goetz, M.D., PDF Research Center at Rush University Medical Center, Chicago, IL, and reviewed by PDF's People with Parkinson's Advisory Council.